The main function of many important organs consists of transporting solutes and water across epithelial cell layers. Regulation of volume and composition of the extracellular fluid, for example, is only possible because of an extremely subtle control of solute and water movement across the epithelial structures of the kidney tubule and of the intestinal wall. Solutes and water must proceed on their passage across epithelial structures either through the epithelial cells or between the cells, through the tight junctions. The latter have recently become the focus of attention since they are thought to be associated with shunt-pathways. However, solute transport linked to metabolic energy is generally considered to go through the epithelial cells and must, therefore proceed across at least two distinct barriers, the membranes on each side of the cell. We do not have enough direct information about the properties of these membranes. Hence, the mechanisms of transcellular transport are not well understood in spite of much work on overall movements across epithelia. The proposed research utilizes a variety of approaches to obtain new and direct information about the individual steps involved in transport of solutes and water across epithelia. Specifically, the movement of ions (Na plus, K plus, and Cl minus) across the outside (mucosal side) and serosal (intracellular side) of the epithelial cells of various tissues will be investigated by measuring unidirectional and net fluxes, and intracellular potentials. The data will be used to formulate an exact functional model of the processes involved in epithelial transport.